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Behavioral and psychological symptoms of dementia (BPSDs) negatively impact the prognosis of dementia patients and increase caregiver distress. The aims of this study were to clarify the differences of trajectories of 12 kinds of BPSDs by disease severity in four major dementias and to develop charts showing the frequency, severity, and associated caregiver distress (ACD) of BPSDs using the data of a Japan multicenter study (J-BIRD). We gathered Neuropsychiatric Inventory (NPI) data of patients with Alzheimer's disease (AD; n = 1091), dementia with Lewy bodies (DLB; n = 249), vascular dementia (VaD; n = 156), and frontotemporal lobar degeneration (FTLD; n = 102) collected during a 5-year period up to July 31, 2013 in seven centers for dementia in Japan. The NPI composite scores (frequency × severity) of 12 kinds of items were analyzed using a principal component analysis (PCA) in each dementia. The factor scores of the PCA were compared in each dementia by disease severity, which was determined with Clinical Dementia Rating (CDR). Significant increases with higher CDR scores were observed in 1) two of the three factor scores which were loaded for all items except euphoria in AD, 2) two of the four factor scores for apathy, aberrant motor behavior (AMB), sleep disturbances, agitation, irritability, disinhibition, and euphoria in DLB, and 3) one of the four factor scores for apathy, depression, anxiety, and sleep disturbances in VaD. However, no increases were observed in any of the five factor scores in FTLD. As dementia progresses, several BPSDs become more severe, including 1) apathy and sleep disturbances in AD, DLB, and VaD, 2) all of the BPSDs except euphoria in AD, 3) AMB, agitation, irritability, disinhibition, and euphoria in DLB, and 4) depression and anxiety in VaD. Trajectories of BPSDs in FTLD were unclear.

Previous studies have suggested that patients with Lewy-body-related dementias might benefit from treatment with the N-methyl D-aspartate receptor antagonist memantine, but further data are needed. Therefore, the efficacy and safety of memantine were investigated in patients with mild to moderate Parkinson's disease dementia (PDD) or dementia with Lewy bodies (DLB). Patients (≥50 years of age) with mild to moderate PDD or DLB were recruited from 30 specialist centres in Austria, France, Germany, the UK, Greece, Italy, Spain, and Turkey. They were randomly assigned to placebo or memantine (20 mg per day) according to a computer-generated list. Patients and all physicians who had contact with them were masked to treatment assignment. No primary endpoint was defined. Safety analyses were done for all patients who took at least one dose of memantine or placebo, and efficacy analyses were done for all patients who had at least one valid postbaseline assessment. This trial is registered with ClinicalTrials.gov, number NCT00855686. Of the 199 patients randomly assigned to treatment, 34 with DLB and 62 with PDD were given memantine, and 41 with DLB and 58 with PDD were given placebo. 159 (80%) patients completed the study: 80 in the memantine group and 79 in the placebo group. 93 patients treated with memantine and 97 patients treated with placebo were included in the efficacy analysis. At week 24, patients with DLB who received memantine showed greater improvement according to Alzheimer's disease cooperative study (ADCS)-clinical global impression of change scores than did those who received placebo (mean change from baseline 3·3 vs 3·9, respectively, difference −0·6 [95% CI −1·2 to −0·1]; p=0·023). No significant differences were noted between the two treatments in patients with PDD (3·6 with memantine vs 3·8 with placebo, −0·1 [−0·6 to 0·3]; p=0·576) or in the total population (3·5 with memantine vs 3·8 with placebo, −0·3 [−0·7 to 0·1]; p=0·120). Neuropsychiatric-inventory scores showed significantly greater improvement in the memantine group than in the placebo group (−4·3 vs 1·7, respectively, −5·9 [−11·6 to −0·2]; p=0·041) in patients with DLB, but not in those with PDD (−1·6 vs −0·1, respectively, −1·4 [−5·9 to 3·0]; p=0·522) or in the total patient population (−2·6 vs 0·4, respectively, −2·9 [−6·3 to 0·5]; p=0·092). In most of the cognitive test scores, ADCS-activities of daily living, and Zarit caregiver burden scores, there were no significant differences between the two treatment groups in any of the study populations. The incidence of adverse events and number of discontinuations due to adverse events were similar in the two groups. The most common serious adverse events were stroke (n=3 in memantine group), falls (n=2 in memantine group; n=1 in placebo group), and worsening of dementia (n=2 in memantine group). Memantine seems to improve global clinical status and behavioural symptoms of patients with mild to moderate DLB, and might be an option for treatment of these patients. Lundbeck.

BackgroundDrug-based therapeutic approaches for Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB) are moderately effective and not always tolerated. Tailoring psychosocial approaches in PDD and DLB may offer additional support and improve outcomes. We adapted home-based, care partner-delivered Cognitive Stimulation Therapy (CST) for individuals with PDD or DLB and their care partners (CST-PD).ObjectivesTo evaluate the feasibility, acceptability, and tolerability of CST-PD.MethodsThis randomised controlled trial used mixed methods, including a process evaluation. People with PDD, DLB or mild cognitive impairment in PD (PD-MCI) and their care partners were randomised to 12 weeks of treatment as usual (TAU) or CST-PD. Outcomes were feasibility of the study conduct (i.e., recruitment, retention rate) and acceptability and tolerability of the intervention. Measures included rating scales, researcher field notes, therapy diaries, and exploratory clinical and care partner efficacy measures.ResultsThe recruitment target was met with 76 consenting participant-dyads. Retention in both arms was high at over 70%. More than 90% of dyads undertook discrete sessions greater than 20 min duration, but the average number of sessions completed was lower than the recommended dose. Acceptability ratings (i.e., interest, motivation and sense of achievement) of the intervention were high. Participants reported no serious adverse events related to the intervention.ConclusionsThe field of psychosocial interventions for PDD and DLB is newly emerging, and we demonstrated that this type of intervention is acceptable and well tolerated. Evaluating its clinical effectiveness in a full-scale randomized controlled clinical trial is warranted.Trial registration numberThe trial is a psychosocial intervention with an allocated ISRCTN number 11455062.

Background Complex visual hallucinations are common in Lewy body dementia (LBD) and can cause significant patient and caregiver distress. Current treatments are primarily pharmacological in nature and have limited efficacy and associated side effects. The objective of this study was to assess the effects of consecutive sessions of transcranial direct current stimulation (tDCS) on visual hallucination frequency and severity in LBD, at short-term and long-term follow-up stages. Methods The study was a randomised, double-blind, placebo-controlled trial involving 40 participants with LBD (M age  = 75.52 years, SD age  = 8.69 years) which was conducted at a single site between November 2013 and December 2017. Participants received two consecutive 20-min sessions of active (0.048 mA/cm 2 ) or placebo tDCS, separated by a 30-min break, over 5 consecutive days. The anodal electrode was applied to the right parietal cortex (P4) and the cathodal electrode was applied to the occipital cortex (O z ). The primary outcome measure was the Neuropsychiatric Inventory (NPI) hallucinations subscale, as completed by a caregiver/informant at baseline and day 5 (short-term) follow-up, and month 1 and month 3 (long-term) follow-up. Secondary outcome measures included visual cortical excitability, as measured using transcranial magnetic stimulation, computerised attentional and visuoperceptual tasks, and measures of global cognition and cognitive fluctuations. Results Complete study data were obtained from 36 participants. There was an overall improvement in visual hallucinations (NPI) for both groups at day 5 relative to baseline, with a medium-to-large effect size; however, compared to placebo, active tDCS did not result in any improvements in visual hallucinations (NPI) at day 5 relative to baseline, or at month 1 or month 3 follow-up time points. Additionally, comparisons of secondary outcome measures showed that active tDCS did not result in any improvements on any measure (visual cortical excitability, attentional and visuoperceptual tasks or cognitive measures) at any time point. Conclusions Repeated consecutive sessions of parietal anodal tDCS, and occipital cathodal tDCS, do not improve visual hallucinations or visuoperceptual function, or alter visual cortical excitability in LBD. Trial registration ISRCTN, ISRCTN40214749 . Registered on 25 October 2013.

Background: Agitation is common in people with dementia, is distressing to patients and stressful to their carers. Drugs used to treat the condition have the potential to cause particularly severe side effects in older people with dementia and have been associated with an increased death rate. Alternatives to drug treatment for agitation should be sought. The study aimed to assess the effects of bright light therapy on agitation and sleep in people with dementia. Methods: A single center randomized controlled trial of bright light therapy versus standard light was carried out. The study was completed prior to the mandatory registration of randomized controls on the clinical trials registry database and, owing to delays in writing up, retrospective registration was not completed. Results: There was limited evidence of reduction in agitation in people on active treatment, sleep was improved and a suggestion of greater efficacy in the winter months. Conclusions: Bright light therapy is a potential alternative to drug treatment in people with dementia who are agitated.

IntroductionParkinson's disease (PD) with mild cognitive impairment (MCI-PD) or dementia (PDD) and dementia with Lewy bodies (DLB) are characterised by motor and ‘non-motor’ symptoms which impact on quality of life. Treatment options are generally limited to pharmacological approaches. We developed a psychosocial intervention to improve cognition, quality of life and companion burden for people with MCI-PD, PDD or DLB. Here, we describe the protocol for a single-blind randomised controlled trial to assess feasibility, acceptability and tolerability of the intervention and to evaluate treatment implementation. The interaction among the intervention and selected outcome measures and the efficacy of this intervention in improving cognition for people with MCI-PD, PDD or DLB will also be explored.Methods and analysisDyads will be randomised into two treatment arms to receive either ‘treatment as usual’ (TAU) or cognitive stimulation therapy specifically adapted for Parkinson's-related dementias (CST-PD), involving 30 min sessions delivered at home by the study companion three times per week over 10 weeks. A mixed-methods approach will be used to collect data on the operational aspects of the trial and treatment implementation. This will involve diary keeping, telephone follow-ups, dyad checklists and researcher ratings. Analysis will include descriptive statistics summarising recruitment, acceptability and tolerance of the intervention, and treatment implementation. To pilot an outcome measure of efficacy, we will undertake an inferential analysis to test our hypothesis that compared with TAU, CST-PD improves cognition. Qualitative approaches using thematic analysis will also be applied. Our findings will inform a larger definitive trial.Ethics and disseminationEthical opinion was granted (REC reference: 15/YH/0531). Findings will be published in peer-reviewed journals and at conferences. We will prepare reports for dissemination by organisations involved with PD and dementia.Trial registration numberISRCTN (ISRCTN11455062).

Aim: To investigate quality of life (QOL) and the effect of memantine treatment in patients with Lewy body dementias. Methods: A secondary analysis of a randomized controlled study in 70 patients with Parkinson’s disease dementia (PDD) or dementia with Lewy bodies (DLB) over 24 weeks using caregiver-rated QOL-Alzheimer’s disease (AD) in domains according to the WHO’s classification of health. Results: Baseline QOL shows lower ratings for body functions over environmental factors in DLB/PDD. Treatment with memantine significantly improves life as a whole compared to placebo and improves total QOL, body function and structure. Conclusion: This study shows that memantine improves QOL in Lewy body dementias. We also demonstrate important QOL patterns which can be used in clinical practice.

Non-motor features of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), such as auditory hallucinations (AH), contribute to disease burden but are not well understood. Systematic review and random-effects meta-analyses of studies reporting AH associated with PD or DLB. Prevalence of visual hallucinations (VH) in identified studies meeting eligibility criteria were included in meta-analyses, facilitating comparison with AH. Synthesis of qualitative descriptions of AH was performed. PubMed, Web of Science and Scopus databases were searched for primary journal articles, written in English, published from 1970 to 2017. Studies reporting AH prevalence in PD or DLB were screened using PRISMA methods. Searches identified 4542 unique studies for consideration, of which, 26 met inclusion criteria. AH pooled prevalence in PD was estimated to be 8.9% [95% confidence interval (CI) 5.3-14.5], while in DLB was estimated to be 30.8% (±23.4 to 39.3). Verbal hallucinations, perceived as originating outside the head, were the most common form of AH. Non-verbal AH were also common while musical AH were rare. VH were more prevalent, with an estimated pooled prevalence in PD of 28.2% (±19.1 to 39.5), while in DLB they were estimated to be 61.8% (±49.1 to 73.0). Meta-regression determined that the use of validated methodologies to identify hallucinations produced higher prevalence estimates. AH and VH present in a substantial proportion of PD and DLB cases, with VH reported more frequently in both conditions. Both AH and VH are more prevalent in DLB than PD. There is a need for standardised use of validated methods to detect and monitor hallucinations.

Dementia with Lewy bodies (DLB), the second most common primary degenerative neurocognitive disorder after Alzheimer disease, is frequently preceded by REM sleep behavior disorders (RBD) and other behavioral symptoms, like anxiety, irritability, agitation or apathy, as well as visual hallucinations and delusions, most of which occurring in 40–60% of DLB patients. Other frequent behavioral symptoms like attention deficits contribute to cognitive impairment, while attention-deficit/hyperactivity disorder (ADHD) is a risk factor for DLB. Behavioral problems in DLB are more frequent, more severe and appear earlier than in other neurodegenerative diseases and, together with other neuropsychiatric symptoms, contribute to impairment of quality of life of the patients, but their pathophysiology is poorly understood. Neuroimaging studies displayed deficits in cholinergic brainstem nuclei and decreased metabolism in frontal, superior parietal regions, cingulate gyrus and amygdala in DLB. Early RBD in autopsy-confirmed DLB is associated with lower Braak neuritic stages, whereas those without RBD has greater atrophy of hippocampus and increased tau burden. αSyn pathology in the amygdala, a central region in the fear circuitry, may contribute to the high prevalence of anxiety, while in attention dysfunctions the default mode and dorsal attention networks displayed diverging activity. These changes suggest that behavioral disorders in DLB are associated with marked impairment in large-scale brain structures and functional connectivity network disruptions. However, many pathobiological mechanisms involved in the development of behavioral disorders in DLB await further elucidation in order to allow an early diagnosis and adequate treatment to prevent progression of these debilitating disorders.

Dementia with Lewy Bodies (DLB) is a neurodegenerative disorder with complex and distressing symptoms, often leading to misdiagnosis and delayed care. While clinical assessments are essential, they may not capture the full breadth of symptomatology experienced by patients and caregivers. Social media, particularly platforms like Reddit, offers patients and caregivers a space to share their challenges in an organic, unstructured way, which can reveal critical insights into symptomatology and caregiving burdens. This study explores how Natural Language Processing (NLP) can be used to analyse this real-world data on DLB symptoms and caregiving challenges. We applied NLP techniques to a large dataset of unstructured text from Reddit discussions. Using the Reddit for Researchers framework, we accessed anonymised comments from the r/Dementia subreddit (44,000 users). Predefined keyword groups focusing on themes related to DLB symptoms, caregiving challenges, medical management, and prognosis were used to query relevant posts. We employed a range of NLP methods, including sentiment analysis to gauge the emotional tone of the posts, and topic modeling (via non-negative matrix factorization) to identify and categorise key themes. We analysed the frequency of different symptom mentions, caregivers' reported challenges, and perceptions of DLB treatment and management. A total of 36,125 comments were analysed, resulting in the identification of several prominent sub-themes. These included descriptions of core DLB symptoms, such as cognitive fluctuations, hallucinations, and motor symptoms, as well as the emotional and physical burden on caregivers. Additionally, analysis revealed frequent mentions of challenges in obtaining a proper diagnosis and navigating healthcare systems, suggesting areas where clinical awareness may need improvement. Topic modeling found caregivers discussing handling hallucinations, managing side effects of medications and planning end of life care. There were also frequent mentions of the emotional impact of DLB, with many caregivers expressing feelings of isolation and frustration with the lack of timely, accurate diagnosis. Applying NLP to social media discussions uncovers valuable insights into the challenges faced by DLB patients and caregivers. This study demonstrates how integrating social media insights into clinical research can provide a deeper understanding of DLB, potentially enhancing diagnosis and treatment strategies.